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NEWS

Osteopontin reveals the early stages of pleural mesothelioma

October 12, 2005 Medical Research News

Researchers at New York University School of Medicine and Wayne State
University have found a molecule that reveals the early stages of pleural
mesothelioma, a chest cancer caused by asbestos. The finding opens the
way to a blood test for the disease, according to a new study published
in the Oct. 13 issue of The New England Journal of Medicine.

An estimated 7.5 million workers in the United States have been exposed
to asbestos and, according to government statistics, it remains a hazard
to some 1.3 million workers in construction and building maintenance.

There has been no way to reliably screen for this type of cancer, particularly
in its early stages when treatment may be more successful. The blood test
could help to monitor people at risk of developing cancer due to asbestos
exposure, says Harvey Pass, M.D., Chief
of the Division of Thoracic Surgery and Thoracic Oncology in the Department
of Cardiothoracic Surgery and Professor of Surgery at NYU School of Medicine,
and the lead author of the study.

"The levels of a protein called osteopontin rise dramatically in
the early stage of this disease," says Dr. Pass. So, he says, "a
rise in the level of this biomarker in workers with past asbestos exposure
may indicate to physicians that these people need to be followed even
more closely for the development of cancer."

Pleural mesothelioma, a cancer that invades the lining
of the chest cavity and the lining of the lungs, usually develops in people
who have been exposed to asbestos, such as foundry workers, pipe fitters,
shipbuilders, miners, electricians, factory workers, firefighters, as
well as construction workers who have used asbestos-containing materials.
It often takes decades to develop.

"There are hotspots across the world where this type of cancer is
clustered," says Dr. Pass. Such clusters are in the Wittenoom district
of Perth, in Western Australia, which has one of the highest incidences
of mesothelioma, he says. Other hotspots include Libby, Montana, regions
in Quebec, Canada, in France and in Turkey

In the new study, Dr. Pass and colleagues found that blood levels of
osteopontin were significantly higher in patients who
had pleural mesothelioma compared to individuals who were exposed to asbestos
and are at risk for developing the cancer.

The study involved 190 patients. Sixty-nine had asbestos-related nonmalignant
disease, such as inflammation which leads to scarring in the lung and
plaques on the lining surrounding the lungs; 45 were current or former
smokers, who had no previous exposure to asbestos; and 76 patients suffered
from pleural mesothelioma and were undergoing surgery.

Those individuals exposed to asbestos for less than 10 years showed the
lowest levels of osteopontin. Those levels doubled in people with more
than 10 years of exposure. The osteopontin levels rose as changes on their
lungs, such as scarring, which were revealed on X rays, became more pronounced.
In the patients with documented pleural mesothelioma, blood levels of
osteopontin jumped--rising six-fold, even in the earliest stage (stage
I) of the disease.

Further research needs to be done to determine the exact levels of the
blood that would be used in screening tests for pleural mesothelioma,
he says, and validation tests are in the planning stages. "What is
crucial," Dr. Pass says, "is that the marker is very encouraging
specifically in asbestos-related early-stage disease."

The outlook for pleural mesothelioma patients who are diagnosed late
is often grim: they may live only 9 to 12 months. Sadly, fewer than 5
percent of mesothelioma cases are detected early. "There are therapies
that will help patients live longer-I would really like to see more patients
found early," says Dr. Pass, who also runs outreach programs to find
people at risk. "Early detection may find patients before they suffer
the ravages of the disease including shortness of breath and pain. At
this point in time, surgery, radiation therapy, chemotherapy, and new
targeted therapies may help extend patients' lives."

Dr. Pass has been exploring surgical approaches in combination with novel
therapies for pleural mesothelioma since 1989, and has also sought to
use molecular biology tools to find an early detection method, as well
as to guide appropriate therapy, for the disease. The discovery of osteopontin
in mesothelioma resulted from the analysis of thousands of genes using
gene expression arrays.

This study was a collaboration between scientists and clinicians at Wayne
State University, the John A. Dingell Veterans Hospital in Detroit, the
Cardinal Bernardin Cancer Center, Loyola University, in Maywood, Illinois
and the Van Andel Research Institute in Grand Rapids, Michigan. The research
was supported in part by a Department of Veterans Affairs Merit Review
Award and by patients' donations.

Dr. Pass recently joined NYU School of Medicine. His previous positions
include Chief, Thoracic Oncology at the Karmanos Cancer Institute, Detroit,
which is affiliated with Wayne State University, and Senior Investigator
and Head of the Thoracic Oncology Section of the National Cancer Institute
in Bethesda, Maryland.

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